18-Methoxycoronardine attenuates nicotine-induced dopamine release and
nicotine preferences in rats.

Glick SD, Maisonneuve IM, Visker KE, Fritz KA, Bandarage UK, Kuehne ME
Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208,
USA.

[Medline record in process]
Two studies were conducted to assess, in vivo, potential anti-nicotinic effects
of the iboga alkaloid ibogaine
and its synthetic congener 18-methoxycoronaridine (18-MC). As previously
demonstrated for ibogaine, using
microdialysis, pretreatment (19h beforehand) with 18-MC (40 mg/kg, i.p.)
significantly attenuated nicotine-
induced dopamine release in the nucleus accumbens of awake and freely moving
rats. In an {*filter*}model of
nicotine self-administration, both ibogaine and 18-MC decreased rats'
preferences for nicotine for at least 24
h. Acutely, during the first hour after administration, ibogaine depressed
responding for water as well as for
nicotine; however, during this same time, 18-MC reduced nicotine intake without
affecting responding for
water. The results suggest that 18-MC might be the prototype of a new treatment
for smoking.

J Med Chem 1998 Nov 5;41(23):4486-91

Modified ibogaine fragments: synthesis and preliminary pharmacological
characterization of 3-ethyl-5-phenyl-1,2,3,4,5, 6-hexahydroazepino[4,5-
b]benzothiophenes.

Efange SMN, Mash DC, Khare AB, Ouyang Q
Departments of Radiology, Medicinal Chemistry, and Neurosurgery, Graduate
Program in Neuroscience,
University of Minnesota, Minneapolis, Minnesota 55455, and Departments of
Neurology and Molecular &
Cellular Pharmacology, University.

[Medline record in process]
Five phenyl-substituted derivatives and analogues of 1,2,3,4,5,
6-hexahydroazepino[4,5-b]indole, 5, a major
fragment of ibogaine (1), were synthesized and tested for binding to monoamine
transporters, the NMDA
receptor-coupled cation channel, and dopamine and opioid receptors. All five
derivatives, 9 and 17a-d,
displayed 8-10-fold higher affinity at the DA transporter than ibogaine and
noribogaine (4). At the serotonin
transporter, two compounds (9 and 17a) exhibited higher potency than ibogaine,
while the rest had weaker
binding affinities than the lead compound. In keeping with their structural
similarity to ibogaine, all five
compounds displayed weak to poor affinity for dopamine D1 and D2 receptors.
However, two compounds,
17a,c, demonstrated moderate binding affinities at dopamine D3 receptors. All
five compounds displayed
weak to poor affinities for &mgr; and kappa opioid receptors and for the NMDA
receptor-coupled cation
channel. Despite the qualitative differences, derivatives and analogues of 5may
serve as useful substitutes
for ibogaine.

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